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CRTC1:TRIM11 cutaneous tumor

Authors: Calvin Tseng, M.D., Zaid Saeed Kamil, M.B.Ch.B.

Deputy Editor-in-Chief: Jonathan D. Ho, M.B.B.S., D.Sc.

Last author update: 15 February 2024

Last staff update: 15 February 2024

Copyright: 2023-2024, PathologyOutlines.com, Inc.

PubMed Search: CRTC1:TRIM11 cutaneous tumor

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Table of Contents

Cite this page: Tseng C, Saeed Kamil Z. CRTC1:TRIM11 cutaneous tumor. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skinmelanocyticCRTC1TRIM11.html. Accessed May 7th, 2024.

Definition / general

Malignant dermal tumor with epithelioid and spindled cells of uncertain origin with partial melanocytic differentiation and CRTC1::TRIM11 translocation

Essential features

Histological features include a dermal / subcutaneous circumscribed tumor composed of fascicles and nests of monomorphic epithelioid and spindle cells with prominent nucleoli divided by delicate collagen septa, no / very rare pigment
Immunohistochemical features include consistent diffuse SOX10 and MITF staining; S100, MelanA and HMB45 stains are variable
Defined by identifying CRTC1::TRIM11 translocation
No evidence of EWSR1 rearrangement
Appears to have at least some malignant potential, although cases and follow up are limited

Terminology

Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion
Not recommended: cutaneous melanocytoma with CRTC1::TRIM11 fusion

ICD coding

ICD-O: 9044/3 - CRTC1:TRIM11 cutaneous tumor
ICD-11: 2C35 - cutaneous sarcoma

Epidemiology

Age: broad range (5 - 87); median age of 42 (Histopathology 2023;82:368)
No clear gender bias (Am J Surg Pathol 2022;46:1457)

Sites

Broad anatomic distribution
Limbs (64%) appear to be involved more often than trunk (20%) and head (2%) based on current case reports (Am J Surg Pathol 2022;46:1457)
2 cases of oral and nasal mucosal involvement (Am J Surg Pathol 2022;46:1457)

Pathophysiology

Exact mechanism of how the CRTC1::TRIM11 fusion transcript causes neoplasia is not known; hypotheses include
- CRTC1::TRIM11 fusion deletes a protein - protein interaction site on TRIM11 that is involved in directing misfolded proteins towards proteasomes for degradation (Cureus 2022;14:e33179)
- CRTC1::TRIM11 fusion retains an interaction site with CREB1, which in turn may drive expression of MITF; MITF acts like an oncogene and can drive MITF synthesis (Am J Surg Pathol 2022;46:1457)

Etiology

Unknown

Clinical features

Discrete, slowly growing, skin colored nodule without pigmentation (Am J Surg Pathol 2022;46:1457)

Diagnosis

Biopsy
Defined by molecular findings

Radiology description

Lobulated lesion on imaging
May be positron emission tomography (PET) avid

Radiology images

Contributed by Aaron Lloyd Hendler, M.D.

PET avid

Prognostic factors

Limited case reports and follow up available but appears more indolent than melanoma and clear cell sarcoma at the time of writing
4 of 48 published cases reported have shown regional or distant metastasis (Am J Surg Pathol 2022;46:1457, Histopathology 2023;82:368, Am J Surg Pathol 2019;43:861, J Cutan Pathol 2024;51:181)
A recent additional case of CRTC1:TRIM11 cutaneous tumor (CTCT) with regional lymph node metastasis was presented at the American Society of Dermatopathology in 2023 (Tseng, et al.: CRTC1::TRIM11 Cutaneous Tumor With Ulceration and Sentinel Lymph Node Metastasis, oral presentation at American Society of Dermatopathology, Oct 2 - 8, 2023)

Case reports

5 year old girl with right upper arm lesion (J Cutan Pathol 2022;49:1025)
27 year old man with fourth finger mass (Cureus 2022;14:e33179)
77 year old man with right thigh lesion (Pathol Int 2019;69:496)

Treatment

Other than complete surgical excision, optimal treatment is unknown

Clinical images

Contributed by Alexandra Easson, M.D.

Ulcerated toe CTCT

Images hosted on other servers:

Arm CTCT

Finger CTCT

Gross description

Circumscribed tumors with pale, firm cut surface without pigmentation
Mean size: 1.4 cm (0.4 - 5.1 cm) (Histopathology 2023;82:368)

Gross images

Contributed by Zaid Saeed Kamil, M.B.Ch.B. and Calvin Tseng, M.D.

Amputation specimen

Microscopic (histologic) description

Morphology is uniform and resembles clear cell sarcoma
Circumscribed, unencapsulated dermal nodule, no / very rare pigment, with only rare cases showing epidermal involvement (J Cutan Pathol 2022;49:1025)
Some cases show extension into subcutis (Am J Surg Pathol 2019;43:861)
Characteristic pattern of nests and intersecting (occasionally herringbone to vaguely palisaded) fascicles of uniform epithelioid to spindled cells with intervening delicate collagen bands (Am J Surg Pathol 2022;46:1457)
Abundant pale eosinophilic cytoplasm, monomorphic nuclei with vesicular chromatin and prominent nucleoli
Mitotic figures present (Am J Surg Pathol 2022;46:1457)
Necrosis reported but uncommon (Am J Surg Pathol 2022;46:1457)
Lymphovascular and perineural invasion uncommon (Am J Surg Pathol 2022;46:1457)
Pigment and multinucleate giant cells may very rarely be seen
A recent case of CTCT with ulceration was reported (Tseng, et al.: CRTC1::TRIM11 Cutaneous Tumor With Ulceration and Sentinel Lymph Node Metastasis, oral presentation at American Society of Dermatopathology, Oct 2 - 8, 2023)

Microscopic (histologic) images

Contributed by Zaid Saeed Kamil, M.B.Ch.B., Stephen M. Smith, M.D. and Calvin Tseng, M.D.

Dermal lesion

Fascicular growth pattern

Monomorphic cells

Vascular invasion

SOX10 diffuse positive

S100 positive

MITF diffuse positive

MelanA negative

HMB45 negative

PRAME negative

Pan-TRK positive

Lymph node metastasis

Lymph node metastasis SOX10

Lymph node weak S100

Negative MelanA and HMB45

Positive stains

SOX10 diffuse positive in all cases (Am J Surg Pathol 2022;46:1457)
MITF diffuse positive in majority of cases (J Cutan Pathol 2022;49:1025)
S100 diffuse positive in 44%, partial positive in 36% (Am J Surg Pathol 2022;46:1457)
MelanA diffuse positive in 9%, partial positive in 52% (Am J Surg Pathol 2022;46:1457)
HMB45 diffuse positive in 4%, partial positive in 52% (Am J Surg Pathol 2022;46:1457)
Ki67 5 - 20% (Am J Surg Pathol 2018;42:382)
Pan-TRK diffuse cytoplasmic positive in 57%, partial cytoplasmic positive in 36% despite lack of TRK mutations (Am J Surg Pathol 2022;46:1457)
TRIM11 diffuse nuclear positive in 94% (Am J Surg Pathol 2022;46:1457)

Negative stains

Molecular / cytogenetics description

CRTC1::TRIM11 fusion (Am J Surg Pathol 2022;46:1457)
No EWRS1 rearrangement (Am J Surg Pathol 2022;46:1457)
No melanoma driver mutations (Am J Surg Pathol 2022;46:1457)
No NTRK fusions despite positivity for pan-TRK immunohistochemistry (Am J Surg Pathol 2018;42:382)

Molecular / cytogenetics images

Contributed by Ian King, Ph.D.

RNA CRTC1::TRIM11 fusion

Images hosted on other servers:

CRTC1::TRIM11 FISH

CRTC1::TRIM11 fusion

Videos

CRTC::TRIM11 cutaneous tumor

Sample pathology report

Skin, amputation, right fifth toe:
- CRTC1::TRIM11 cutaneous tumor (see comment)
- Comment: The neoplasm is composed of intersecting fascicles and nests of relatively uniform epithelioid and spindled cells with intervening bands of fibrocollagenous stroma. The neoplastic cells have abundant amounts of amphophilic to eosinophilic cytoplasm and moderately pleomorphic nuclei with prominent nucleoli. Mitotic figures including deep mitoses are identified. There is no evidence of necrosis, lymphovascular invasion or perineural invasion. The neoplastic cells are diffusely positive for SOX10, patchy positive for S100 and negative for MelanA and HMB45. Molecular analysis demonstrated the presence of CRTC1::TRIM11 fusion. Overall, the features are compatible with the recently described CRTC1::TRIM11 cutaneous tumor. Based on the limited reported cases and limited follow up data, the clinical course was indolent in most of the reported cases. However, 4 of the reported cases presented with regional nodal metastasis or distant metastasis as of January 2024. The available data at the time of this report suggest that these tumors have at least some malignant potential.

Differential diagnosis

Clear cell sarcoma:
- Predominantly affects adults ages 30 - 40s
- Often deeper location (associated with tendons or aponeuroses)
- Infiltrative growth
- May have clear cells and melanin pigment
- Wreath-like multinucleated tumor giant cells
- More consistently expresses S100, MelanA and HMB45
- Has ESWR1 translocations, most commonly EWSR1::ATF1 or EWSR1::CREB1
- Lacks CRTC1::TRIM11 fusion
- More aggressive behavior
Melanoma:
- In situ component (may not be present for previously excised melanoma, metastatic melanoma or primary dermal melanoma)
- Infiltrative growth
- Pleomorphic cytology
- Pigment production
- More consistently expresses S100, MelanA and HMB45 (other than in desmoplastic melanoma)
- PRAME positive
- Has melanoma driver mutations
- Lacks CRTC1::TRIM11 fusion
- More aggressive behavior
Spitz tumor:
- Junctional component of vertically oriented nests and Kamino bodies may be present
- More consistently expresses S100, MelanA and HMB45
- Molecular analysis shows HRAS mutation or kinase fusions
- Lacks CRTC::TRIM11 fusion
Cellular blue nevus:
- Component of dendritic blue nevus is often present
- Pigmented melanophages present
- Necrosis is absent
- Mitotic activity is usually low
- Consistently positive for MelanA and HMB45
- Molecular shows GNAQ or GNA11 mutations
- Lacks CRTC1::TRIM11 fusion
Myoepithelial tumors:
- Myxoid stroma may be present
- EMA positive
- Keratin, p63, SMA and calponin may be positive
- MITF negative
- EWSR1 rearrangements in syncytial variant
- Lacks CRTC1::TRIM11 fusion
Epithelioid schwannoma:
- MITF negative
- 40% show loss of INI1 (Am J Surg Pathol 2017;41:1013)
- Lacks CRTC1::TRIM11 fusion
Epithelioid MPNST:
- Increased pleomorphism
- MITF negative
- Subset shows loss of INI1
- Lacks CRTC1::TRIM11 fusion
PEComa:
- Irregular interface with dermal collagen
- Mitotic figures sparse or absent
- Express HMB45, MelanA as well as SMA, desmin and caldesmon
- SOX10 negative (Am J Surg Pathol 2015;39:826)
- Deletion of TSC2 gene
- Lacks CRTC1::TRIM11 fusion
MITF pathway activated melanocytic tumors:
- Infiltrative growth
- Prominent clear cytoplasm
- May have areas of higher grade morphology
- Can have mitotic activity and perineural invasion
- Usually expresses either MelanA or HMB45
- Has ACTIN::MITF or MITF::CREM fusions
- Lacks CRTC1::TRIM11 fusion

Additional references

J Cutan Pathol 2019;46:810, J Cutan Pathol 2021;48:915, WHO Classification of Tumours Editorial Board: Skin Tumours, 5th Edition, 2024

Board review style question #1

A superficial dermal tumor with the above histology is identified. IHC shows diffuse SOX10 positivity, diffuse MITF positivity, partial S100 positivity, partial MelanA positivity and partial HMB45 positivity. PRAME IHC is negative. Molecular investigations identify a CRTC1::TRIM11 fusion. Is it important to differentiate this entity from melanoma and clear cell sarcoma and why?

No, as this entity currently appears to behave similarly to melanoma and clear cell sarcoma
No, as this entity is currently thought to be a subtype of melanoma
Yes, as this entity currently appears to behave less aggressively than melanoma and clear cell sarcoma
Yes, as this entity currently has specific targeted treatments available

Board review style answer #1

C. Yes, as this entity currently appears to behave less aggressively than melanoma and clear cell sarcoma. Based on follow up data available as of October 2023, CRTC1:TRIM11 cutaneous tumor (CTCT) appears to be a low grade malignancy that behaves less aggressively than typical melanomas and clear cell sarcomas. Answer B is incorrect because CTCT has not had melanoma driver mutations identified as of October 2023. Answer A is incorrect because CTCT appears to behave less aggressively than melanoma and clear cell sarcoma based on follow up data available as of October 2023. Answer D is incorrect because no targeted treatment has been identified for CTCT as of October 2023.

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Reference: CRTC1:TRIM11 cutaneous tumor

Board review style question #2

Of the following features, which is typical of CRTC1:TRIM11 cutaneous tumor (CTCT)?

Absence of mitotic activity
Presence of an epidermal component
Presence of CRTC1::TRIM11 fusion
Presence of infiltrative growth

Board review style answer #2

C. Presence of CRTC1::TRIM11 fusion. CRTC1:TRIM11 cutaneous tumor (CTCT) is defined by the CRTC1:TRIM11 fusion, which has not yet been identified in other entities. Answer B is incorrect because the majority of CTCT cases do not show an epidermal component. Answer D is incorrect because the majority of CTCT are well circumscribed. Answer A is incorrect because CTCT show mitotic activity.

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Reference: CRTC1:TRIM11 cutaneous tumor

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